Oxidative Stress and Lung Fibrosis: Towards an Adverse Outcome Pathway.

Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due to oxidative stress and chronic inflammation are central features of lung fibrosis. Chronic cigarette smoking causes oxidative stress and is a major risk factor for lung fibrosis.

Changes in Biomarkers of Exposure and Potential Harm in Smokers Switched to Vuse Vibe or Vuse Ciro Electronic Nicotine Delivery Systems.

Electronic nicotine delivery systems (ENDS) have the potential to provide nicotine to tobacco consumers while reducing exposure to combustion-related toxicants. Here, we report changes in biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH) in smokers who completely switched to Vuse Vibe and Vuse Ciro ENDS products, or to smoking abstinence in a randomized, controlled clinical study. Thirteen BoE (12 urinary and one blood) that indicate exposure to harmful and potentially harmful toxicants (HPHCs) were evaluated at baseline on day 5.

Biomarkers of Exposure and Potential Harm in Two Weeks of Smoking Abstinence: Changes in Biomarkers of Platelet Function, Oxidative Stress, and Inflammation.

: Chronic cigarette smoking is a major risk factor for many serious diseases. While complete cessation of smoking is the best option to reduce harm from smoking, adverse impacts of smoking on health could persist for several years after cessation. Therefore, Biomarkers of Potential Harm (BoPH) are useful in interim evaluations of the beneficial effects of smoking cessation or switching to potentially lower-risk tobacco products.

Cigarette and ENDS preparations differentially regulate ion channels and mucociliary clearance in primary normal human bronchial 3D cultures.

Cigarette smoking is known to disrupt the normal mucociliary function of the lungs, whereas the effect of electronic nicotine delivery systems (ENDS) is not completely understood. This study aimed to compare the effects of acute exposure of primary normal human bronchial epithelial (NHBE) 3D cultures at air-liquid interface to combustible cigarette and ENDS preparations on mucociliary function, including ion channel function, ciliary beat frequency (CBF), and airway surface liquid (ASL) height. Differentiated NHBE cultures were exposed to whole smoke-conditioned media (WS-CM) or total particulate matter (TPM) prepared from 3R4F reference cigarettes, whole aerosol-conditioned media (ACM) or e-TPM generated from a marketed ENDS product, or nicotine alone.

Optimization of Normal Human Bronchial Epithelial (NHBE) Cell 3D Cultures for in vitro Lung Model Studies.

Robust in vitro lung models are required for risk assessment to measure key events leading to respiratory diseases. Primary normal human bronchial epithelial cells (NHBE) represent a good lung model but obtaining well-differentiated 3D cultures can be challenging. Here, we evaluated the ability to expand primary NHBE cells in different culture conditions while maintaining their 3D culture characteristics such as ciliated and goblet cells, and ion channel function.

Complete artificial saliva alters expression of proinflammatory cytokines in human dermal fibroblasts.

Complete artificial saliva (CAS) is a saliva substitute often used as a vehicle for test articles, including smokeless tobacco products. In the course of a study employing normal adult human dermal fibroblasts (HDFa) as a model in vitro, we discovered that CAS as a vehicle introduced a significant change in the expression of proinflammatory cytokines. To determine the effects of CAS on gene expression, real-time quantitative reverse-transcriptase PCR gene array analysis was used.

Differential cell-specific cytotoxic responses of oral cavity cells to tobacco preparations.

To examine the effects of standardized (reference) tobacco preparations on human oral cavity cells, two oral squamous cell carcinoma cell lines (101A, 101B) and normal human gingival epithelial cells (HGEC) were treated with cigarette smoke total particulate matter (TPM), smokeless tobacco extracted with complete artificial saliva (ST/CAS), or whole-smoke conditioned media (WS-CM). EC-50 values, as determined by sulforhodamine B assays, varied among the cell types and agents. When normalized to nicotine content, cytotoxicity for WS-CM and TPM was higher compared to that observed with ST/CAS.

Nanosized paclitaxel particles from supercritical carbon dioxide processing and their biological evaluation.

The rapid expansion of a supercritical solution into a liquid solvent (RESOLV) technique with benign supercritical carbon dioxide was applied to obtain aqueous suspended nanoparticles of the highly potent anticancer drug paclitaxel. The paclitaxel nanoparticles were protected from agglomeration by using a known nontoxic stabilization agent. The aqueous suspended paclitaxel nanoparticles of different average particle sizes were evaluated in vitro against human breast cancer cells.

C60-fullerenes: detection of intracellular photoluminescence and lack of cytotoxic effects.

We have developed a new method of application of C60 to cultured cells that does not require water-solubilization techniques. Normal and malignant cells take-up C60 and the inherent photoluminescence of C60 is detected within multiple cell lines. Treatment of cells with up to 200 microg/ml (200 ppm) of C60 does not alter morphology, cytoskeletal organization, cell cycle dynamics nor does it inhibit cell proliferation.